Restorative Neurology and Neuroscience - Volume 34, issue 4

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ISSN 0922-6028 (P)

ISSN 1878-3627 (E)

Impact Factor 2018: 2.101

This interdisciplinary journal publishes papers relating the plasticity and response of the nervous system to accidental or experimental injuries and their interventions, transplantation, neurodegenerative disorders and experimental strategies to improve regeneration or functional recovery and rehabilitation.

Experimental and clinical research papers adopting fresh conceptual approaches are encouraged. The overriding criteria for publication are novelty, significant experimental or clinical relevance and interest to a multidisciplinary audience.

Abstract: Purpose: The neural mechanisms that support aphasia recovery are not yet fully understood. Our goal was to evaluate longitudinal changes in naming recovery in participants with posterior cerebral artery (PCA) stroke using a case-by-case analysis. Methods: Using task based and resting state functional magnetic resonance imaging (fMRI) and detailed language testing, we longitudinally studied the recovery of the naming network in four participants with PCA stroke with naming deficits at the acute (0 week), sub acute (3–5 weeks), and chronic time point (5–7 months) post stroke. Behavioral and imaging analyses (task related and resting state functional connectivity)…were carried out to elucidate longitudinal changes in naming recovery. Results: Behavioral and imaging analysis revealed that an improvement in naming accuracy from the acute to the chronic stage was reflected by increased connectivity within and between left and right hemisphere “language” regions. One participant who had persistent moderate naming deficit showed weak and decreasing connectivity longitudinally within and between left and right hemisphere language regions. Conclusions: These findings emphasize a network view of aphasia recovery, and show that the degree of inter- and intra- hemispheric balance between the language-specific regions is necessary for optimal recovery of naming, at least in participants with PCA stroke.
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Abstract: Background : Aphasia is an acquired deficit in the ability to communicate through language. Noninvasive neuromodulation offers the potential to boost neural function and recovery, yet the optimal site of neuromodulation for aphasia has yet to be established. The right posterolateral cerebellum is involved in multiple language functions, interconnects with left-hemisphere language cortices, and is crucial for optimization of function and skill acquisition, suggesting that cerebellar neuromodulation could enhance aphasia rehabilitation. Objective : To provide preliminary behavioral and functional connectivity evidence from healthy participants that cerebellar neuromodulation may be useful for rehabilitation of aphasia. Methods : In Experiment…1, 76 healthy adults performed articulation and verbal fluency tasks before and after anodal, cathodal or sham transcranial direct current stimulation (tDCS) was applied over two cerebellar locations (anterior, right posterolateral). In Experiment 2, we examined whether anodal tDCS over the right posterolateral cerebellum modulated resting-state functional connectivity in language networks in 27 healthy adults. Results : TDCS over the right posterolateral cerebellum significantly improved phonemic fluency. Cerebellar neuromodulation increased functional connectivity between the cerebellum and areas involved in the motor control of speech, and enhanced the correlations between left-hemisphere language and speech-motor regions. Conclusion : We provide proof-of-principle evidence that cerebellar neuromodulation improves verbal fluency and impacts resting-state connectivity in language circuits. These findings suggest that the cerebellum is a viable candidate for neuromodulation in people with aphasia.
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Abstract: Background: Post-stroke aphasia syndromes as a clinical entity arise from the disruption of brain networks specialized in language production and comprehension due to permanent focal ischemia. This approach to post-stroke aphasia is based on two pathophysiological concepts: 1) Understanding language processing in terms of distributed networks rather than language centers and 2) understanding the molecular pathophysiology of ischemic brain injury as a dynamic process beyond the direct destruction of network centers and their connections. While considerable progress has been made in the past 10 years to develop such models on a systems as well as a molecular level, the…influence of these approaches on understanding and treating clinical aphasia syndromes has been limited. Objective & Methods: In this article, we review current pathophysiological concepts of ischemic brain injury, their relationship to altered information processing in language networks after ischemic stroke and how these mechanisms may be influenced therapeutically to improve treatment of post-stroke aphasia. Conclusion: Understanding the pathophysiological mechanism of post-stroke aphasia on a neurophysiological systems level as well as on the molecular level becomes more and more important for aphasia treatment, as the field moves from standardized therapies towards more targeted individualized treatment strategies comprising behavioural therapies as well as non-invasive brain stimulation (NIBS).
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Abstract: Background/Objective: Transcranial direct current stimulation (tDCS) can enhance or diminish cortical excitability levels depending on the polarity of the stimulation. One application of non-invasive brain-stimulation has been to modulate a possible inter-hemispheric disinhibition after a stroke. This disinhibition model has been developed mainly for the upper extremity motor system, but it is not known whether the language/speech-motor system shows a similar inter-hemispheric interaction. We aimed to examine physiological evidence of inter- and intra-hemispheric connectivity changes induced by tDCS of the right inferior frontal gyrus (IFG) using arterial-spin labeling (ASL) MRI. Methods: Using an MR-compatible DC-Stimulator, we applied…anodal stimulation to the right IFG region of nine healthy adults while undergoing non-invasive cerebral blood flow imaging with arterial-spin labeling (ASL) before, during, and after the stimulation. All ASL images were then normalized and timecourses were extracted in regions of interest (ROIs), which were the left and right IFG regions, and the right supramarginal gyrus (SMG) in the inferior parietal lobule. Two additional ROIs (the right occipital lobe and the left fronto-orbital region) were taken as control regions. Results: Using regional correlation coefficients as a surrogate marker of connectivity, we could show that inter-hemispheric connectivity (right IFG with left IFG) decreased significantly (p < 0.05; r-scores from 0.67 to 0.53) between baseline and post-stimulation, while the intra-hemispheric connectivity (right IFG with right SMG) increased significantly (p < 0.05;r-scores from 0.74 to 0.81). A 2 × 2 ANOVA found a significant main effect of HEMISPHERE (F(8) = 6.83, p < 0.01) and a significant HEMISPHERE-by-TIME interaction (F(8) = 4.24, p < 0.05) in connectivity changes. The correlation scores did not change significantly in the control region pairs (right IFG with right occipital and right IFG with left fronto-orbital) over time. Conclusion: Using an MR-compatible DC stimulator we showed that ASL-MRI can detect tDCS-induced modulation of brain connectivity within and between hemispheres. These findings might affect trial designs focusing on modulating the non-dominant hemisphere to enhance language/speech-motor functions.
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Abstract: The functional deficit after a focal brain lesion is determined by the localization and the extent of the tissue damage. Since destroyed tissue usually cannot be replaced in the adult human brain, improvement or recovery of neurological deficits can be achieved only by reactivation of functionally disturbed but morphologically preserved areas or by recruitment of alternative pathways within the functional network. The visualization of disturbed interaction in functional networks and of their reorganization in the recovery after focal brain damage is the domain of functional imaging modalities such as positron emission tomography (PET). Longitudinal assessments at rest and during activation…tasks during the early and later periods following a stroke can demonstrate recruitment and compensatory mechanisms in the functional network responsible for complete or partial recovery of disturbed functions. Imaging studies have shown that improvements after focal cortical injury are represented over larger cortical territories. It has also been shown that the unaffected hemisphere in some instances actually inhibits the recovery of ipsilateral functional networks and this effect of transcallosal inhibition can be reduced by non-invasive brain stimutation. Non-invasive brain stimulation (NIBS) can modulate the excitability and activity of targeted cortical regions and thereby alter the interaction within pathologically affected functional networks; this kind of intervention might promote the adaptive cortical reorganization of functional networks after stroke. In poststroke aphasia several studies attempted to restore perilesional neuronal activity in the injured left inferior frontal gyrus by applying excitatory high frequency repetitive transcranial magnetic stimulation (rTMS) or intermittent theta burst stimulation (iTBS) or anodal transcranial direct current stimulation (tDCS), but most NIBS studies in poststroke aphasia employed inhibitory low frequency rTMS for stimulation of the contralesional pars triangularis of the right inferior frontal gyrus (BA 45) in order to reduce right hemisphere hyperactivity and transcallosal inhibition on the left Broca’s area. While most studies reported single cases or small case series with chronic poststroke aphasia without any control condition, only a few controlled studies including sham stimulation were performed in chronic stage after stroke. In one controlled randomized study changes in PET activation pattern in the subacute course were related to the clinical improvement. In this “proof-of-principle” study the shift of the activation pattern to the dominant hemisphere induced by inhibitory rTMS over the right inferior frontal gyrus could be demonstrated in the PET activation studies and correlated to improved performance in aphasia tests. NIBS might be a treatment strategy which could improve the effect of other rehabilitative efforts.
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Abstract: Purpose: Aphasia—acquired loss of the ability to understand or express language—is a common and debilitating neurological consequence of stroke. Evidence suggests that transcranial magnetic (TMS) or direct current stimulation (tDCS) can significantly improve language outcomes in patients with aphasia (PWA). However, the relative efficacy between TMS and tDCS has not yet been explored. Mechanistic and methodological differences, patient inclusion/exclusion criteria and experimental designs may influence observed treatment benefits. Methods: We conducted a systematic review and meta-analyses of TMS and tDCS treatment studies in PWA. Standard mean difference (SMD) for changes in picture naming accuracy was estimated; pooled…SMDs were compared using a random-effects model. Results: Eight TMS (N = 143) and 8 tDCS studies (N = 140) met our inclusion criteria. Pooled SMDs of 0.448 (p < 0.001) in favor of TMS, and 0.395 (p < 0.001) in favor of tDCS were found. Between-subject designs were more common in subacute and within/crossover designs in chronic patients. TMS SMDs were significant in both chronic (SMD = 0.348) and subacute (SMD = 0.667) populations while those for tDCS were significant in chronic (SMD = 0.320) but not in subacute (SMD = 0.283) PWA. Conclusions: The magnitude of treatment effects appears to be consistent between TMS and tDCS in PWA. Larger-scale clinical trials should further substantiate our findings.
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Abstract: Purpose: In order to promote alertness and awareness in patients with severe disorders of consciousness (DOC) frontal near infrared laser stimulation (N-LT) or transcranial focused shock wave therapy (F-SWT) might be an option. The study compared both techniques in severe chronic DOC patients. Methods: Sixteen DOC patients were allocated to two groups (A and B). A three week baseline either followed a frontal N-LT (0,1 mJ/mm2 , 10 min per session), five times a week over four weeks (group A), or a F-SWT (0,1 mJ/mm2 , 4000 stimuli per session) three times a week over four weeks (group B). The…primary variable was the revised Coma Recovery Scale (r-CRS, 0–23), blindly assessed. Results: Both groups improved in the r-CRS over time, but revealed no differences between groups. One patient of group B had a focal seizure in the third therapy week. One patient with akinetic mutism improved most and three patients with global hypoxia did not improve at all. Conclusions: Both options might be an option to increase alertness and awareness of chronic DOC patients. An akinetic mutism seems to be a positive and severe cerebral hypoxia a negative predictor. Epileptic seizures are a potential unwanted side effect. More clinical studies are warranted.
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